This invention relates to a bicyclo[3.3.0]octane derivative and a process for producing the same.
9(0)-methano-.DELTA..sup.6(9.alpha.) -PGI.sub.1 has a potent platelet aggregation inhibiting action. For example, its action is comparable to chemically unstable PGI2, when human platelet is employed, and it is a compound which can be utilized as a therapeutic or preventive for various diseases of circulatory organs (see the test examples shown below).
In the prior art, as the process for producing 9(0)-methano-.DELTA..sup.6(9.alpha.) -PGI.sub.1, there have been known (a) the process in which it is produced through the 14 steps using PGE.sub.2 as the starting material [Preliminary Text for Lectures in 103rd Annual Meeting in Pharmaceutical Society of Japan, p. 156, (1983)] and (b) the process in which it is produced from 1,3-cyclooctadiene through 19 steps [Preliminary Text for Lectures in 103rd Annual Meeting in Pharmaceutical Society of Japan, p. 157, (1983)]. The former process has the drawback that the starting material is expensive, while the latter process that the desired product is formed as a racemic mixture. Further, both processes (a) and (b) are also disadvantageously very low in the overall yield.
On the other hand, (4'-alkoxycarbonyl-1'-alkenyl)-cis-bicyclo[3.3.0]octene derivative can be led to 9(0)-methano-.DELTA..sup.6(9.alpha.) -PGI.sub.1 and its various derivatives by highly selective reduction of the double bonds of the .alpha.-chains, elimination of the protective group for hydroxyl group and hydrolysis of the ester.
Further, (4'-alkoxycarbonyl-1'-alkenyl)-cis-bicyclo[3.3.0]octene derivative can easily be led to various carbacyclines stereospecifically by 1,4-reduction of conjugated diene.
The above carbacyclines are synthesized according to any of the processes by the Wittig reaction to cis-bicyclo[3.3.0]octane-3-one derivatives [e.g. W. Skuballa and H. Vorbruggen, Angew. Chem. Int. Ed. Engl., 20, 1046 (1981) W. Skuballa et al. (Schering AG), Eur. Pat. 11, 591; Ger. Offen. No. 2,845,770.7; '83 Inflammation Seminar-Prostaglandin Program Preliminary Text, Shinsaku Kobayashi, at p. 37].
However., according to this process, a mixture of 5-E derivative [a] and 5-Z derivative [b] is obtained, and separation of the 5-E derivative [a] which is useful as pharmaceutical remains as the great problem in the synthetic process. ##STR3##